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1.
  • Enroth, Stefan, et al. (författare)
  • Effects of Long-Term Storage Time and Original Sampling Month on Biobank Plasma Protein Concentrations
  • 2016
  • Ingår i: EBioMedicine. - 2352-3964. ; 12, s. 309-314
  • Tidskriftsartikel (refereegranskat)abstract
    • The quality of clinical biobank samples is crucial to their value for life sciences research. A number of factors related to the collection and storage of samples may affect the biomolecular composition. We have studied the effect of long-time freezer storage, chronological age at sampling, season and month of the year and on the abundance levels of 108 proteins in 380 plasma samples collected from 106 Swedish women. Storage time affected 18 proteins and explained 4.8–34.9% of the observed variance. Chronological age at sample collection after adjustment for storage-time affected 70 proteins and explained 1.1–33.5% of the variance. Seasonal variation had an effect on 15 proteins and month (number of sun hours) affected 36 proteins and explained up to 4.5% of the variance after adjustment for storage-time and age. The results show that freezer storage time and collection date (month and season) exerted similar effect sizes as age on the protein abundance levels. This implies that information on the sample handling history, in particular storage time, should be regarded as equally prominent covariates as age or gender and need to be included in epidemiological studies involving protein levels.
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2.
  • Matar, Amal (författare)
  • Considering a Baby? Responsible Screening for the Future : Ethical and social implications for implementation and use of preconception expanded carrier screening in Sweden
  • 2019
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • Preconception expanded carrier screening is a novel technology that involves the offer of a screening test for many recessive diseases (via an expanded screening panel) to prospective parents, with no priori risk. Test positive couples have a number of reproductive choices; prenatal diagnosis and aborting affected fetus, IVF and preimplantation genetic diagnosis, sperm or ovum donation or simply accept the risk. The test had been piloted in studies and can potentially be implemented in Europe. Therefore, it seemed pertinent to evaluate stakeholders’ perspectives on ethical and social implications of implementing and using preconception ECS in Sweden.Two main stakeholders were examined; healthcare professionals and health policymaking experts, via a mix of qualitative methods for data collection and data analysis. In Study I, we employed in-depth interviews to collect data and content analysis to analyze it. In Studies III and IV, expert interviews were used to gather data while thematic analysis was utilized to interpret it. Furthermore, in Study II, an ethical concept namely; reproductive autonomy, was critically discussed within a setting that expects a couple to make a conjoint reproductive decision about preconception ECS, while each partner still upholds his or her individual autonomy.The main findings of the empirical studies (Studies I, III and IV) echo to a great extent the prevailing ethical and social debates associated with the novel technology. Respondents expressed concerns with reproductive autonomy, medicalization, prioritization of health resources, discrimination and long term societal changes. Furthermore, respondents emphasized the importance to observe Swedish values, such as human dignity, equality and solidarity, when assessing a preconception ECS program. In addition, they described practicalities of implementation and political considerations that are pertinent to the Swedish context. Finally, some respondents recognized the advantages of reduced suffering and decrease in fetal anomalies and abortion as a consequence of preconception ECS.Study II, proposed a notion of couple autonomy, where certain demands if met, a couple’s reproductive decision can be accepted by healthcare staff as autonomous.The findings, in this thesis, steer towards non implementation of preconception ECS in its current status within the publicly-funded healthcare system in Sweden. This is because healthcare providers and experts were of the opinion that it would not solve a medical need, threaten Swedish values and use up resources extensively.
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4.
  • Petzold, Martin, et al. (författare)
  • Towards an Ambient Assisted Living User Interaction Taxonomy
  • 2013
  • Ingår i: CHI '13 Extended Abstracts of the ACM International Conference on Human Factors in Computing Systems. - New York : ACM Press. - 9781450318990 ; , s. 49-54
  • Konferensbidrag (refereegranskat)abstract
    • Extensive research in the field of ambient assisted living (AAL) provides profound knowledge about the design of AAL systems. However, more generic design characteristics for user interaction have not been formalized for this domain yet. Thus, we propose to develop a domain specific taxonomy for the design of user interaction in AAL systems. We adopted a systematic taxonomy development approach that combines an empirical and a pseudo-conceptual strategy. Six co-researchers from different disciplines conduct the iterative research process. Next to AAL systems existing taxonomies in the field of human-computer interaction are analyzed following the Delphi method. In this paper we present our research process and preliminary results from the first iteration. The final taxonomy allows classification and should support the analysis of user interaction utilized in AAL systems. Furthermore, it can deal as a practical design guideline.
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5.
  • Boiso, Samuel, et al. (författare)
  • RapidHIT for the purpose of stain analyses – An interrupted implementation
  • 2017
  • Ingår i: Forensic Science International. - : Elsevier. - 1875-1768 .- 1875-175X. ; 6:Supplement C, s. e589-e590
  • Tidskriftsartikel (refereegranskat)abstract
    • Rapid DNA instruments have in recent years been developed, enabling analysis of forensic samples with a minimum of human intervention. Initially intended for fast handling of reference samples, such as samples from suspects in booking suites, attention shifted to include crime scene samples. The aim of this study was to determine whether or not the RapidHIT System (IntegenX) is fit for crime scene samples. The first runs gave very poor results, which was found to be due to an incorrect firmware setting leading to no or just minute amounts of amplicons being injected for electrophoresis. After solving this problem, 28 full runs (seven samples each) applying NGM SElect Express were performed comprising various amounts of blood on cotton swabs. Six of the runs failed completely, four due to cartridge leakage and in two runs the PCR mix was not injected. For 155 samples with 1–5ÎŒL blood (volumes for which complete DNA profiles are expected), 119 samples (77%) gave complete DNA profiles. Among the most serious failures were incorrect allele calling and leakage of DNA extract or PCR product. Other general issues were failure to export results, anode motor breakdown and broken capillary array. Due to the encountered problems with software, hardware and cartridges, together with the low success rate, it was decided not to continue towards implementation of the RapidHIT System in casework.
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6.
  • Yu, Feifan, et al. (författare)
  • An affibody-adalimumab hybrid blocks combined IL-6 and TNF-triggered serum amyloid A secretion in vivo
  • 2014
  • Ingår i: MABS. - 1942-0862. ; 6:6, s. 1598-1607
  • Tidskriftsartikel (refereegranskat)abstract
    • In inflammatory disease conditions, the regulation of the cytokine system is impaired, leading to tissue damages. Here, we used protein engineering to develop biologicals suitable for blocking a combination of inflammation driving cytokines by a single construct. From a set of interleukin (IL)-6-binding affibody molecules selected by phage display, five variants with a capability of blocking the interaction between complexes of soluble IL-6 receptor a (sIL-6R alpha) and IL6 and the co-receptor gp130 were identified. In cell assays designed to analyze any blocking capacity of the classical or the alternative (trans) signaling IL-6 pathways, one variant, Z(IL-6_13) with an affinity (K-D) for IL-6 of similar to 500 pM, showed the best performance. To construct fusion proteins ("AffiMabs") with dual cytokine specificities, Z(IL-6_13) was fused to either the N-or C-terminus of both the heavy and light chains of the anti-tumor necrosis factor (TNF) monoclonal antibody adalimumab (Humira (R)). One AffiMab construct with Z(IL-6_13) positioned at the N-terminus of the heavy chain, denoted Z(IL-6_13)-HCAda, was determined to be the most optimal, and it was subsequently evaluated in an acute Serum Amyloid A (SAA) model in mice. Administration of the AffiMab or adalimumab prior to challenge with a mix of IL-6 and TNF reduced the levels of serum SAA in a dose-dependent manner. Interestingly, the highest dose (70 mg/kg body weight) of adalimumab only resulted in a 50% reduction of SAA-levels, whereas the corresponding dose of the Z(IL-6_13)-HCAda AffiMab with combined IL-6/TNF specificity, resulted in SAA levels below the detection limit.
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7.
  • Lind-Halldén, Christina, et al. (författare)
  • Genetic Variation in the Syntaxin-Binding Protein STXBP5 in Type 1 von Willebrand Disease Patients
  • 2020
  • Ingår i: Thrombosis and Haemostasis. - : F K Schattauer Verlag Gmbh. - 0340-6245. ; 118:8, s. 1382-1389
  • Tidskriftsartikel (refereegranskat)abstract
    • von Willebrand factor (VWF) levels in healthy individuals and in patients with type 1 von Willebrand disease (VWD) are influenced by genetic variation in several genes, for example, VWF , ABO and STXBP5 . Here, we comprehensively screen for STXBP5 variants and investigate their association with type 1 VWD in Swedish patients and controls. The coding region of the STXBP5 gene was re-sequenced in 107 type 1 VWD patients and the detected variants were genotyped in the type 1 VWD population and a Swedish control population (464 individuals). The functional effects of missense alleles were predicted in silico and the pattern of genetic variation in STXBP5 was analysed. Re-sequencing of 107 type 1 VWD patients identified three missense and three synonymous variants in the coding sequence of STXBP5 . The low-frequency missense variants rs144099092 (0.005) and rs148830578 (0.029) were predicted to be damaging, but were not accumulated in patients. No other rare candidate mutations were detected. STXBP5 showed a high level of linkage disequilibrium and a low overall nucleotide diversity of π = 3.2 × 10 −4 indicating intolerance to variants affecting protein function. Three previously type 1 VWD-associated single nucleotide polymorphisms were located on one haplotype that showed an increased frequency in patients versus controls. No differences in messenger ribonucleic acid abundance among haplotypes could be found using Genotype-Tissue Expression project data. In conclusion, a haplotype containing the STXBP5 Asn436Ser (rs1039084) mutation is associated with type 1 VWD and no rare STXBP5 mutations contribute to type 1 VWD in the Swedish population.
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8.
  • Ajalloueian, Fatemeh, et al. (författare)
  • Constructs of electrospun PLGA, compressed collagen and minced urothelium for minimally manipulated autologous bladder tissue expansion
  • 2014
  • Ingår i: Biomaterials. - 0142-9612 .- 1878-5905. ; 35:22, s. 5741-5748
  • Tidskriftsartikel (refereegranskat)abstract
    • Bladder regeneration based on minced bladder mucosa in vivo expansion is an alternative to in vitro culturing of urothelial cells. Here, we present the design of a hybrid, electrospun poly(lactic-co-glycolide) (PLGA) - plastically compressed (PC) collagen scaffold that could allow in vivo bladder mucosa expansion. Optimisation of electrospinning was performed in order to obtain increased pore sizes and porosity to consolidate the construct and to support neovascularisation and tissue ingrowth. Tensile tests showed an increase in average tensile strength from 0.6 MPa for PC collagen to 3.57 MPa for the hybrid construct. The optimised PLGA support scaffold was placed between two collagen gels, and the minced tissue was distributed either on top or both on top and inside the construct prior to PC; this was then cultured for up to four weeks. Morphology, histology and SEM demonstrated that the construct maintained its integrity throughout cell culture. Cells from minced tissue migrated, expanded and re-organised to a confluent cell layer on the top of the construct after two weeks and formed a multilayered urothelium after four weeks. Cell morphology and phenotype was typical for urothelial mucosa during tissue culture. (C) 2014 Elsevier Ltd. All rights reserved.
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9.
  • Aulin, Cecilia, 1979- (författare)
  • Extracellular Matrix Based Materials for Tissue Engineering
  • 2010
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • The extracellular matrix is (ECM) is a network of large, structural proteins and polysaccharides, important for cellular behavior, tissue development and maintenance. Present thesis describes work exploring ECM as scaffolds for tissue engineering by manipulating cells cultured in vitro or by influencing ECM expression in vivo. By culturing cells on polymer meshes under dynamic culture conditions, deposition of a complex ECM could be achieved, but with low yields. Since the major part of synthesized ECM diffused into the medium the rate limiting step of deposition was investigated. This quantitative analysis showed that the real rate limiting factor is the low proportion of new proteins which are deposited as functional ECM. It is suggested that cells are pre-embedded in for example collagen gels to increase the steric retention and hence functional deposition. The possibility to induce endogenous ECM formation and tissue regeneration by implantation of growth factors in a carrier material was investigated. Bone morphogenetic protein-2 (BMP-2) is a growth factor known to be involved in growth and differentiation of bone and cartilage tissue. The BMP-2 processing and secretion was examined in two cell systems representing endochondral (chondrocytes) and intramembranous (mesenchymal stem cells) bone formation. It was discovered that chondrocytes are more efficient in producing BMP-2 compared to MSC. The role of the antagonist noggin was also investigated and was found to affect the stability of BMP-2 and modulate its effect. Finally, an injectable gel of the ECM component hyaluronan has been evaluated as delivery vehicle in cartilage regeneration. The hyaluronan hydrogel system showed promising results as a versatile biomaterial for cartilage regeneration, could easily be placed intraarticulary and can be used for both cell based and cell free therapies.
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10.
  • Yang, Xianyan, et al. (författare)
  • Intra-bone marrow injection of trace elements co-doped calcium phosphate microparticles for the treatment of osteoporotic rat
  • 2017
  • Ingår i: Journal of Biomedical Materials Research. Part A. - 1549-3296 .- 1552-4965. ; 105:5, s. 1422-1432
  • Tidskriftsartikel (refereegranskat)abstract
    • Osteoporotic femur fractures are the most common fragility fracture and account for approximately one million injuries per year. Local intervention by intra-marrow injection is potentially a good choice for preventing osteoporotic bone loss when the osteoporotic femoral fracture was treated. Previously, it was shown that trace element co-doped calcium phosphate (teCaP) implants could stimulate osteoporotic bone marrow mesenchymal stem cell activity in vitro and bone regeneration in femoral bone defects in osteoporotic animal models. They hypothesized that local intra-marrow injection of teCaP particles could improve bone function because the teCaP can sustain release of biologically essential inorganic minerals and improve bone remodeling in osteoporosis. The teCaP and CaP particles were synthesized in simulated body fluid with and without adding silicon, zinc and strontium ions. Female rats (8 months) were ovariectomized (OVX) or sham-operated, and then intervened in the femoral marrow space at 12 months old. Groups include: (1) saline water; (2) CaP particles; and (3) teCaP particles. After 2-3 months of intervention, the sham groups showed higher bone mineral density (MBD) in the femur, and teCaP group increased the BMD in the OVX groups. The compressive strength of the OVX-teCaP group was significantly higher than that in the OVX-CaP group. Significant differences between OVX-teCaP and OVX-CaP groups were found for bone mineral microarchitecture, bone mineral density, and trace mineral content, but not for feces composition. These results confirm the teCaP particles could suppress osteoporotic bone loss by local intramarrow injection. Therefore, this biomaterial could be used as a next-generation combination treatment for osteoporotic trauma and osteoporosis itself.
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